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Pharmacology > Gout > Flashcards

Gout Flashcards

1
Q

Gout

A

Characterized by acute attacks of joint inflammation, resulting from deposition of urate crystals in the joint or other tissues.

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2
Q

Pathogenesis of gout

A 
Crystalization of urate in the synovial fluid and joint tissue.
Crystal-induced inflammatory response.
PMNs phagocytize crystals.
Release of kinins and lysosomal enzymes.
Tophi
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3
Q

Tophi

A

uric acid crystal deposits, usually on joint tendons and skin

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4
Q

Hyperuricemia

A

Serum urate > 7 in men and > 5.7 in women

Serum uric acid may fall during acute gouty attack

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5
Q

Epidemiology of gout

A

US: males more than females. Estrogen promotes uric acid renal excretion, female gout is typically post-menopausal.
Prevalence increases with age, probably due to decreased renal function.
Age >40, alcohol intake, renal insufficiency.
Drug therapy for HTN, CHF, renal insufficiency (diruetics, low dose ASA)
Gout rises due to metabolic syndromes (obesity)
Enzyme defects (HGPRT-ase deficiency, increased PRPP synthetase activity)

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6
Q

Diagnosing

A 
Joint aspirate (urate crystals in joint fluid)
Biopsied tophus (contains urate crystals)
Clinical diagnosis based on criteria
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7
Q

Clinical presentation

A

Go to bed feeling well, wake up due to pain, pain becomes severe, cannot tolerate touch, often unable to carry out ADL or sleep due to pain.

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8
Q

Clinical diagnosis (6 out of 12)

A 
More than 1 attack of acute arthritis
Maximal inflammation within 1 day
Monoarticular
Joint redness
1st metatarsophalangeal joint painful or swollen
Unilateral attack
Suspected tophus
Hyperuricemia
Asymmetric swelling within joint on xray
Subcortical cysts without erosions on xray
Negative culture of joint fluid
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9
Q

Extrarenal excretion of uric acid

A

100 mg/day eliminated via GI tract through secretions. Degraded by bacteria. GI excretion can greatly increase in renal failure.

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10
Q

PRPP-synthetase

A

PRPP-synthetase is backbone for production of purines, will produce more uric acid

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11
Q

HGPRT-ase

A

We recycle purines within the body, if we have a deficiency of HGPRT-ase, will not be able to recycle and will be eliminated into hypoxanthine which can be further metabolized into uric acid (through xanthine oxidase). Allopurinal and Febuxostat block xanthine oxidase.

Body is very good at recycling purines released with cell death instead of creating uric acid.

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12
Q

Acute gout attack management

A

Treat with NSAIDs, corticosteroids, or colchicine. May need to use more than one agent for severe pain or multiple joints.
Ice for inflammation
Maybe opiods

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13
Q

Colchicine

A

Effective, but may be more toxic than NSAIDs or corticosteroids

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14
Q

Indomethacin

A

NSAID, 50 mg TID/QID for 2-3 days, taper off.

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15
Q

Naproxen

A

NSAID. 750 mg load dose, 500 mg BID, taper.

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16
Q

Sulindac

A

NSAID. 200 mg BID, taper.

17
Q

Ketorolac

A

NSAID. 30-60 mg IM one-time dose.

18
Q

Corticosteroids

A

Use for elderly, C/I to NSAIDs or Colchicine, transplant patients.

19
Q

Prednisone

A

20-50 mg/day (0.5mg/kg/d) until relief.
High dose 2-5 days, taper 7-10 days.
High dose 5-10 days then stop.

20
Q

Triamcinolone acetonide

A

Corticosteroid. Sustained release. 60 mg IM with or without PO prednisone

21
Q

Intra-articular corticosteroids with lidocaine

A

Systemic therapy CI, do with a joint aspirate.

22
Q

Colchicine

A

Anti-inflammatory.
30% cleared through kidney.
CI: P-gp inhibitors (DDI), P-gp thought to limit GI absorption, inhibitors may cause accumulation.

CYP450 34A DDI:
Cimetidine, ketoconazole, statins, erythromycin, grapefruit juice.
Protease inhibitors: fosamprenavir, retonavir.

Reduce colchicine dose or don’t use at all.

23
Q

Colchicine treatment

A

Oral tablets are 0.6 mg.
High dose 0.6-1.2 mg initially, continue one tab an hour until:
Pain relief, diarrhea or GI symptoms, or cumulative dose of 4.8 mg.

Low dose: 1.2 mg initially, followed by 0.6 mg 1 hour later and then another 0.6 mg BID 12 hours after until gout attack resolves.

Begin within 36 hours of onset.

Onset of action delayed, should see by hour 18, pain relief by 48 hours.

24
Q

Colchicine SE

A

GI effects (dose-related): nausea, vomiting, diarrhea.
Hepatotoxicity
Nephrotoxicity
Neurotoxicity
Myopathy: check CK Q6 months with CrCl <50 for use of 0.5mg/day
Bone marrow depression
Alopecia

25
Q

Requirements for maintenance for chronic gout

A

Decrease serum uric acid <6 or 5. Slowly decrease.
Frequent attacks.
Tophi formation.
Joint destruction.
Progression of renal impairment (CKD > stage 2)
Past renal stone formation

26
Q

Maintenance options

A

Diet
Allopurinol, Febuxostat
Uricosurics
Prophy 6 months
NSAIDs: low dose (first line) prophy + PPI
Colchicine prophy
Prednisone prophy (second line) <10mg/day

Continue for 6 months, or 3 months after goal urate levels with no tophi, or 6 months after goal urate levels with few tophi.

27
Q

Diet for gout

A 
Avoid/decrease purine foods
Decrease alcohol
Avoid high fructose-sweetened drinks
Limit carbs
Vit C
Weight reduction
Fluid intake
28
Q

Allopurinol

A

Xanthine oxidase inhibitor.
Oxypurinol is active metabolite, long half life (18-30 hours). Reabsorbed in kidney, reduce dose in renal impairment.
Once daily dosing.
Start with low dosing and colchicine or NSAID. Increase slowly to goal uric acid level.
Consider genetic testing with Han Chinese, Thai and Korean patients with CKD > stage 3. Risk for AHS.

Serum uric acid falls within 1-2 days, max 7-10 days. Improvement within 6 months. Continue therapy.

SE: hematological (rare), rashes (discontinue at first sign of a rash, start at lower dose if mild), Stevens-Johnson syndrome with renal insufficiency or genetic carriers. Hypersensitivity, hepatotoxicity (check LFTs in first year), GI nausea, vomitting, diarrhea. Long term risk of cataracts (more than 3 years and 400 gm cumulative dose)

29
Q

Febuxostat

A

Xanthine oxidase inhibitor.
More expensive, more potent (inhibits both oxidized and reduced forms of xanthine oxidase).
Can use smaller doses.
Start low dose, increase after 2 weeks if uric acid levels high.
99% protein bound, active metabolites.
Weak inhibitor of CYP2D6

Fewer SE, LFT elevation 5-6%, arthralgias, rash, nausea.

30
Q

Colchicine prophylaxis

A

Does not decrease uric acid, does not prevent tophi formation, has adverse effects.

Prevents gouty attacks during initiation of xanthine oxidase inhibitors or uricosurics.

Dose: 0.6 mg daily or BID, lower dose with CrCl <50?

31
Q

Xanthine oxidase inhibitors

A

No comparison between forms. 1st line treatment.
Good for renal impairment, tophi, renal stones, induction chemo.

Use concomitant pharmacologic anti-inflammatory agent.

Decrease serum uric acid levels. Increase hypoxanthine and xanthine, eliminated by renal. Reduces crystalluria. No anti-inflammatory effect, no uricosuric effect.

32
Q

Probenecid

A

Uricosuric. Alternative first line ULT treatment. Can add on to XOI if uric acid not at target.
Good for underexcretors of uric acid. Inhibits proximal tubulue reabsorption of uric acid.

First determine 24 hour clearance. Normal <800, overproducer >1000.

Use in patients with CrCl >50 who are clearly underproducers of uric acid and no risk for renal stones. Don’t use with stone history.

Start low dose. Decrease dose after uric acid lowered. Maximal excretion is 30-60 minutes after dose, increase fluid intake.

SE: headache, hypersensitivity reaction, GI, renal stones, rare: nephrotic syndrome, hepatic necrosis, blood dyscrasias

33
Q

Fenofibrate

A

Lowers cholesterol/lipids. Weak uricosuric effect

34
Q

Losartan

A

Weak uricosuric effect

35
Q

Disadvantages of probenecid

A 
Do not use with renal imairment CrCl <50.
Not with renal stone history.
Uricosuric effect antagonized by ASA
Exacerbate attacks in early therapy
No anti-inflammatory effect
DDI: MTX, penicillins, cephalosporins.
36
Q

Lesinurad (Zurampic)

A

New drug. Used in combo with XOI. Lots of renal ADR is used alone.
30% excreted unchanged in urine.
Induces CYP3A4.
Metabolized by CYP2C9.

37
Q

Pegloticase

A

Very expensive, for resistant gout attacks. Recombinant enzyme similar to one that mammals do not have.

IV dose.
Premedicate with antihistamines and corticosteroids.
Start NSAID, corticosteroid or colchicine prophy 1 week prior to initiation.

Can form antibodies to it. Caution in CHF, G6PD deficiency

38
Q

Rilonacept (Arcolyst)

A

Not approved for gout, but has been used during initial urate-lowering therapy.

Pharmacology (11 decks)

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